CN101232807B - Compositions having a high antiviral and antibacterial efficacy - Google Patents

Compositions having a high antiviral and antibacterial efficacy Download PDF

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Publication number
CN101232807B
CN101232807B CN2005800477946A CN200580047794A CN101232807B CN 101232807 B CN101232807 B CN 101232807B CN 2005800477946 A CN2005800477946 A CN 2005800477946A CN 200580047794 A CN200580047794 A CN 200580047794A CN 101232807 B CN101232807 B CN 101232807B
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acid
composition
virus
polymerization
application
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CN101232807A (en
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J·L·富尔斯
T·J·泰勒
P·S·福克斯
N·D·罗杰斯
H·E·汤纳
J·达尔顿
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Henkel AG and Co KGaA
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Dial Corp
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/02—Acyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/74—Synthetic polymeric materials
    • A61K31/765—Polymers containing oxygen
    • A61K31/78—Polymers containing oxygen of acrylic acid or derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Antimicrobial compositions having a rapid antiviral and antibacterial effectiveness, and a persistent antiviral effectiveness, are disclosed. The antimicrobial compositions contain (a) a disinfecting alcohol, (b) an organic acid, and (c) water, wherein the composition has a pH of about 5 or less.

Description

Composition with high antiviral and antibacterial efficacy
Cross reference to related application
The application requires the U.S. Provisional Patent Application No.60/634 of submission on December 9th, 2004, the U.S. Provisional Patent Application No.60/634 that on December 9th, 464 and 2004 submitted to, 483 right.
Invention field
The present invention relates to antimicrobial compositions, it has the antibacterial effect of quick and lasting antiviral effect and quick wide spectrum.More particularly, the present invention relates to antimicrobial compositions, comprise pure and mild (b) organic acid of (a) sterilization.Said (a) and combination (b) can provide collaborative Gram-negative and Gram-positive bacteria and/or deactivation synergistically or the elimination virus (such as rhinovirus and rotavirus) of reducing, and this is based on said organic acid log P (water-octanol distribution coefficient).Said composition has been cut down (for example greater than 99%) naked virus crowd and Gram-negative and gram-positive bacteria number significantly in 1 minute.
Background of invention
In daily life, health runs into many microbiological effects.Particularly with environment in the contact of different microorganism possibly cause mammalian diseases, possibly be serious disease.For example microbial contamination possibly cause numerous disease, comprises food poisoning, streptococcal infection, anthrax (skin), the ringworm of the foot, herpes labialis, conjunctivitis (" blood-shoot-eye illness "), COxsackie-virus (hand-foot-and-mouth syndrome), croup, diphtheria (skin), ebolic Hemorrhagic fever and impetigo without limitation.
As everyone knows, clean body part (for example washing one's hands) and crust (for example work top and sump) and can reduce said micropopulation significantly, comprise pathogene.Therefore, thus clean skin and other animate and inanimate surface is to remove the primary protection that such pathogene minimizes the risk that infects from these surfaces to reduce micropopulation.
Virus is the main pathogen type that relates to.Virus infections belongs to the maximum reason to of human morbidity, estimates to come from virus infections at the human diseases of developed country's 60% above acute attack.In addition, virus almost infects at each biology of occurring in nature, and high viral infection rate takes place in all mammals (animal that comprises the mankind, pet, domestic animal and zoo).
Virus is demonstrating many-sided difference aspect structure and lifetime.At FundamentalVirology, 4th Ed., Eds.Knipe & Howley, Lippincott Williams &Wilkins, Philadelphia, PA has specified virus stock, its structure, lifetime and virus infections pattern in 2001.
In brief, virion is intrinsic obligate parasite, and the transmission genetic material and the enough information of encoding guarantee its propagation between cell thereby it has taken place to develop.In citation form, virus is made up of the nucleic acid small fragment that is wrapped in the simple protein shell.Between the virus maximum difference with envelope virus and nonenveloped virus, that is, comprise or do not comprise lipid-bimolecular tunic respectively.
Virus is only bred in living cells.The major obstacle that virus runs into is to be able to get into cell, and cell is by membrane protective, and the thickness of cell membrane can be equal to the size of virus.For penetration cell, virus at first must be attached to cell surface.Virus is that to the specificity major part of certain type of cell it is attached to the lip-deep ability of said specific cells.For the importantly lasting contact of virus infections host cell, the said ability of virus is the characteristic of virus and host cell with the cell surface that is contacted.The fusion of virus and host cell membrane has obtained complete virion, and perhaps, in some cases, only virulent infectious nucleic acid gets into said cell.Therefore,, importantly promptly kill the virus of contacting skin, and on skin or crust, lasting antiviral activity is provided ideally so that the control virus infections in order to control virus infections.
For example known rhinovirus, influenza virus and adenovirus cause respiratory tract infection.Rhinovirus is the member of picornavirus family, and picornavirus is " nonenveloped virus " that lacks adventitia.Why the human rhinovirus is because its special nasopharynx zone that adapts to is the most important pathogene of adult and children's common cold by such name.102 kinds of rhinovirus serotypes are formally arranged.Separation is from most of picornavirus acid labile of human respiratory system, and this lability becomes confirms rhinoviral characteristic.
Rhinovirus infection is propagated interpersonal through direct contact viral pollution respiratory apparatus secretion.Usually, this contact is with the form that directly contacts with contaminated surface, rather than through sucking airborne virion.
Rhinovirus possibly survive several hours on environmental surfaces after initial pollution; Infect easily and propagate to the contact of finger, if be used for rubbing one's eyes or contacting schneiderian membrane after the contaminated recently finger through the contact and the contaminated environmental surfaces of finger.Therefore, should the pollution of virus to skin and environmental surfaces be minimized, propagate the risk that infects so that reduce to general groups.
Some gastrointestinal infection also cause by virus, particularly rotavirus.For example Norwalk virus causes feeling sick, vomits (following diarrhoea sometimes) and gastrospasm.This infection is normally propagated between the people through being in direct contact with.The acute hepatitis A virus infections similarly can be by transmitting direct contact infection through hand to hand, mouthful in one's hands or hanging drop between the infected and non-immune individuality, or when infected individuals not touches the solid that hepatitis A virus pollutes, pass through indirect contact transmission.Many other virus infectionses are propagated similarly.Through will or removing and significantly to reduce the risk of propagating such virus infections from the inactivation of virus of hand and other environmental surfaces.
Usually phenol/pure the bactericidal agent of family expenses is effective aspect the sterilization of the environmental surfaces of polluting, but lacks lasting viricidal activity.Washing one's hands is being fruitful aspect the finger of sterilization pollution, lacks persistent puzzlement but also receive.These shortcoming explanations need improved virucidal compositions, and it has the lasting activity to virus (like rhinovirus and rotavirus).
Antimicrobial personal care composition is known in this area.Particularly the antibiotic cleaning composition is known commodity, and it is commonly used to clean skin and hand, arm and the face of eliminating the bacterium that exists on the skin, particularly user.
Bactericidal composition is used for for example being used by individual consumer in health-care industry, food service industry, meat industry and private sector.The extensive use of bactericidal composition shows the attention of consumer to bacterial community on the control skin.The pattern of bactericidal composition provides significantly and reduces bacterial population rapidly and do not have the adverse side effect relevant with toxicity and skin irritation with wide spectrum ground.In Patent No 6,107, such bactericidal composition is disclosed in 261 and 6,136,771, said document is quoted at this respectively.
One type of antibiotic personal care composition is the hand disinfectant gel.This based composition mainly is medical worker's be used to sterilize hand and finger.The hand disinfectant gel is used in one's hands and finger and friction, allows said composition to evaporate from skin.
The hand disinfectant gel contains a high proportion of alcohol (like ethanol).Under the pure high percentage that in said gel, exists, itself has just played the effect of bactericidal agent said alcohol.In addition, said alcohol promptly evaporates, and has avoided wiping or has cleaned the skin with said disinfectant Gel Treatment.The hand disinfectant gel that contains at high proportion alcohol (that is, about 40% of said composition or bigger percentage by weight) is killing bacteria enduringly.
The antibiotic cleaning composition contains antimicrobial activity, surfactant and other multiple compositions, for example dyestuff, spices, pH regulator agent, thickener, skin conditioning agent etc. usually in moisture and/or pure carrier.Multiple different types of antibacterial agent has been used for the antibiotic cleaning composition.The instance of antibacterial agent comprises that Bisguanidine (for example; The Chlorhexidine diglucoside), the compounds of biphenol compound class, benzyl alcohols, three halogen hexichol ureas, quaternary ammonium compound class, ethoxylation phenols and phenol, like the substituted Phenol compounds of halogen, (promptly like PCMX; To between chloro--xylenol) and triclosan (promptly; 2,4,4 '-three chloro-2 '-dihydroxy diphenyl ether).Show the antibacterial activity of wide model based on the antimicrobial compositions of this antibacterial agent, from low to high, depended on the microorganism that to control and specific antimicrobial compound.Most of coml antimicrobial compounds generally provide and are low to moderate appropriate antibacterial activity, do not have the antiviral activity of report.
The log that antimicrobial acivity is evaluated as the micropopulation that antimicrobial compositions provides reduce or optionally percentage reduce.For specific time of contact, be generally 15 seconds-5 minutes, it is preferred that the log of 1-3 reduces, the log of 3-5 reduces most preferred, however being less than that 1 log reduces is that bottom line is preferred.Therefore, for the broad-spectrum micro-organisms in the short contacting time, the log that highly preferred antimicrobial compositions shows 3-5 reduces.
Virus control has proposed the more problem of difficulty with respect to bacterial control.Through sufficiently reducing bacterial flora, risk of bacterial infections is reduced to acceptable level.Therefore, the antibiotic fast inhibition of expectation.Yet for virus, not only expectation suppresses fast, but also needs lasting antiviral activity.This difference is not enough to reduce infection for no other reason than that reduce virus groups.In theory, single virus can cause infection.Therefore, for antiviral Cleasing compositions effectively, need or expect complete basically and lasting antiviral activity at least.
U.S. Patent number 6,110,908 disclose surperficial preservative, contain C 2-3Alcohol, the fatty acid and the vancide ZP that dissociate.
U.S. Patent number 5,776,430 disclose surperficial antimicrobial cleansing agent, contain Chlorhexidine and ethanol.Composition contains the methylated spirit of the 50%-60% weight of having an appointment and the Chlorhexidine of about 0.65%-0.85% weight.Composition is to be suitable for skin, smears skin, again cleaning and removing from the skin.
European patent application 0 604 848 discloses the hand disinfectant of gel-type, contains the alcohol of antimicrobial, about 40%-90% weight, and combination weight is no more than the polymer and the thickener of 3% weight.Gel is to wipe on hand, makes its evaporation so that the hand of sterilization to be provided.Disclosed composition does not usually provide sanitation and hygiene immediately to handle, and lasting antimicrobial efficacy is not provided.
Generally, the hand disinfectant gel contains usually: (a) combination of the ethanol of at least 60% weight or lower alcohol such as ethanol and isopropyl alcohol, and (b) water, (c) gel polymer such as crosslinked polyacrylate material reach (d) other compositions, like skin conditioning agent, aromatic etc.The consumer uses the hand disinfectant gel to come to sterilize effectively hand, do not have or after a while, and with soap and washing hand, or the surface of hand disinfectant gel wiping at hand.Current coml hand disinfectant gel depends on high-caliber alcohol and sterilizes and evaporate, and has therefore received infringement.Especially, because the volatility of ethanol, after the use, main antimicrobial can not be retained on the skin, therefore fails to provide lasting anti-microbial effect.
Determining alcohol is lower than at 60% o'clock, and ethanol is not thought preservative.Therefore, contain be less than 60% alcohol composition in, exist other Antimicrobe compound so that antimicrobial acivity to be provided.Yet, not previous disclosedly do not address this problem, the composition components in the promptly this antimicrobial compositions provides control of microorganisms.Therefore, for contain reduce determining alcohol preparation for, provide quick antimicrobial effect and lasting antimicrobial benefit the selection of antimicrobial be difficult.
U.S. Patent number 6,107,261 and 6,136,771 disclose the bactericidal composition that highly effectively contains the antimicrobial of phenol.These patents disclose, and the composition that solves bacterial control problem on control skin and the watch face is useless for control virus.
U.S. Patent number 5,968,539,6,106,851 and 6,113,933 disclose the bactericidal composition of pH for about 3-about 6.Composition contains antibacterial agent, anion surfactant and proton donor.
Antiviral composition is disclosed as deactivation or eliminates Causative virus, comprises rhinovirus, rotavirus, influenza virus, parainfluenza virus, Respiratory Syncytial Virus(RSV) and norwalk virus, also is known.For example U.S. Patent number 4,767, and 788 disclose the glutaric acid deactivation or elimination virus comprises rhinoviral purposes.U.S. Patent number 4,975,217 disclose the composition that contains organic acid and anion surfactant, are used for the preparation of soap or washing lotion, to control virus.United States Patent (USP) discloses 2002/0098159 and discloses proton and give agent (proton donating agent) and surfactant (comprising antibiotic surfactant) influence antiviral purposes with antibacterial properties.
U.S. Patent number 6,034,133 disclose and have contained malic acid, citric acid and C 1-6The viricidal hand cleanser of alcohol.U.S. Patent number 6,294,186 disclose the combination of benzoic acid analog such as salicylic acid and selected slaine, effectively antiviral (comprising rhinovirus).U.S. Patent number 6,436,885 disclose the combination of antibacterial agent known under pH2-5.5 and 2-Pyrrolidone-5-carboxylic acid, to provide antibiotic and antiviral properties.
Organic acid in the personal wash compositions also is disclosed.For example, WO 97/46218 is used for antimicrobial cleansing compositions with organic acid or salt, hydrotrote, triclosan and the hydrogeneous solvent that WO 96/06152 discloses in the surfactant matrix.These publications are useless for antiviral property.
People such as Hayden, Antimicrobial Agents and Chemotherapy, 26:928-929 page or leaf (1984) discloses the hand cleanser that has residual viricidal activity through use, and the hand-right-hand that interrupts the rhinovirus flu is propagated.In type rhinoviral confirmed in deactivation, the hand cleanser that contains 2% glutaric acid was more more effective than placebo.Yet publication discloses, and the washing lotion that contains glutaric acid is ineffectually for the rhinovirus serotype of wide spectrum.
The thin paper (tissue) that kills the virus is designed for the individual who is caught a cold and infect, and it contains citric acid, malic acid and NaLS, is known.People such as Hayden, Journal of InfectiousDiseases, 152:493-497 page or leaf (1985), however reported and used with killing the virus mass treatment or untreated thin paper, hand adversary's that can blocking virus propagation.Therefore, in the propagation that prevents the rhinovirus flu, not having significant benefits is owing to the composition that mixes the thin paper that kills the virus.
Useful effect is difficult to obtain in effective antimicrobial compositions of bacterium with virus, because the intrinsic difference of bacterium and virus.Although the antimicrobial cleansing product that current existence is a large amount of; (for example has the multiple product form; The soap of deodorizing, hard surface cleaner and surgery disinfectant), such antimicrobial products is mixed antimicrobial, for example phenolic compounds usually; And/or for the surfactant of uncomfortable suitable (harsh), it possibly become dry and chafe tissue.Ideally, personal cleansing product is cleaning skin leniently, produces a little or does not produce stimulation, and do not allow skin over-drying after frequent the use.
Therefore; The microorganism that need suppress wide spectrum at short notice highly effectively comprises the antimicrobial compositions of virus and gram-positive bacteria and Gram-negative bacteria; Wherein composition can provide the antiviral activity of lasting and wide spectrum, and is gentle for skin.Prove that the personal care product who improves gentleness and increase virus and bacterium minimizing level is provided by antimicrobial composition of the present invention.
Summary of the invention
The present invention be directed to antimicrobial compositions, it provides the quick and lasting antivirus action and the quick and actual minimizing of gram-positive bacteria and Gram-negative bacteria in being less than about 1 minute clock time.More particularly, the present invention relates to contain the alcohol, (b) organic acid of (a) sterilization and (c) antimicrobial compositions of water, wherein said composition has about 5 or lower pH.This composition is surfactant and effective antibacterial agent such as phenol and antibacterial agent quaternary ammonium that does not contain the cleansing surfactants that have a mind to add such as anion, cation and both sexes.
Irrelevant with organic acid log P, this antimicrobial compositions provides the quick and lasting control of nonenveloped virus, reaches broad-spectrum sterilization fast.Yet in one embodiment, organic acid has the water-octanol distribution coefficient that is expressed as log P, be lower than 1, and composition has shown synergistic activity for nonenveloped virus.In another embodiment, organic acid has 1 or bigger log P, and composition has shown synergistic activity to bacterium.And in another embodiment, organic acid contains log P and equals 1 or bigger organic acid less than 1 first organic acid and log P, and said composition has shown synergistic activity to nonenveloped virus and bacterium.
Therefore; One aspect of the present invention provides antimicrobial compositions; It is that the bacterium that highly effectively kills wide spectrum comprises gram-positive bacteria and Gram-negative bacteria such as aurococcus, hog cholera sramana (family name) bacterium, Escherichia coli and pneumobacillus; The virus that deactivation simultaneously or elimination are harmful to human health, the virus of particularly nonencapsulated virus such as acid labile and particularly rhinovirus, the pico+ribonucleic acid+virus of other acid labile and rotavirus.
Another aspect of the present invention provides liquid, antimicrobial compositions, contains:
(a) alcohol of the sterilization of about 25%-75% weight such as C 1-6Alcohol;
(b) kill the virus one or more organic acids of effective dose; With
(c) water,
Wherein said composition has about 5 or lower pH.
And another aspect of the present invention provides antimicrobial compositions, has shown actual wide spectrum and lasting virus control, and the control of actual broad spectrum of bacteria.
Another aspect of the present invention has provided the antimicrobial compositions with antibacterium and antiviral activity, comprises alcohol, (b) organic acid of (a) sterilization and (c) water, and organic acid directly is used for skin and can transdermal, for example hydrophobic monocarboxylic acid; Polybasic carboxylic acid; Acid or its mixture with polymerization of a plurality of carboxyls, phosphate radical, sulfonate radical and/or sulfate radical part, wherein composition has about 5 or lower pH.Such organic acid has usually and is lower than 1 log P, and composition is effectively for the bacterium of wide spectrum, and nonenveloped virus has been shown synergistic activity.
And another aspect of the present invention provides and has antibiotic and antimicrobial compositions antiviral activity, and pure and mild (b) that comprise (a) sterilization is selected from hydrophobic monocarboxylic acid; Polybasic carboxylic acid; Acid or the organic acid of its mixture with polymerization of a plurality of carboxyls, phosphate radical, sulfonate radical and/or sulfate radical part, and (c) water, wherein said composition has about 5 or lower pH, and organic acid has 1 or bigger log P.These compositions provide effective and lasting control nonenveloped virus, and gram-positive bacteria and Gram-negative bacteria have been shown synergistic activity.
Another aspect of the present invention provides antimicrobial compositions; At least 4-30 second comprises that to the virus of nonenveloped virus such as acid labile rhinovirus serotype such as rhinovirus Ia, rhinovirus 2, rhinovirus 14 and rhinovirus 4 and rotavirus serotype such as rotavirus Wa have shown the log minimizing after contact.5 hours antimicrobial compositions also provide at least 3 log to reduce to nonenveloped virus after using time of contact of 30 seconds, and 6 hours antimicrobial compositions also provide at least 2 log minimizing to nonenveloped virus after using time of contact of 30 seconds.In certain embodiments, antimicrobial compositions provides 2 log minimizing for nonenveloped virus, and is high to about 8 hours.
And antimicrobial compositions is provided in another aspect of the present invention, after 30 seconds time of contact, gram-positive bacteria (that is staphylococcus aureus) has been shown at least 2 log minimizing.
And another aspect of the present invention has provided antimicrobial compositions, after 30 seconds time of contact, Gram-negative bacteria (that is Escherichia coli) has been shown at least 2.5 log minimizing.
Another aspect of the present invention is to carry the confession consumer goods that are the basis with antimicrobial compositions of the present invention; For example, skin cleaner, body splash, surgical scrub, Wound nursing agent, hand disinfectant gel, disinfectant, collutory, pet shampoo, crust disinfectant, washing lotion, ointment, emulsifiable paste etc.Composition of the present invention can be to need the product of flush away or the product that stays after using.Preferably, composition is stayed on the skin, the evaporating volatile component.Composition is to let the people joyful and non-stimulated to skin on the aesthetics.
Further aspect of the present invention provides quick control comprises people's structural wide spectrum in animal tissue virus and the method for gram-positive bacteria and Gram-negative flora; Through with composition contact tissue of the present invention such as corium time enough; For example about 15 seconds to 5 minutes or longer, to reduce bacterium and virus groups level level to expectation.Further aspect of the present invention is a composition, and it provides lasting virus control to animal tissue.
And another aspect of the present invention provides treatment or prevent virus-mediated disease and the method for the illness that caused by rhinovirus, pico+ribonucleic acid+virus, adenovirus, rotavirus, herpes virus, Respiratory Syncytial Virus(RSV) (RSV), coronavirus, enterovirus and other nonenveloped viruses.
And another aspect of the present invention provides composition and method, with blocking virus from the propagation to lived surface such as application on human skin of life and abiotic surface is arranged.Provide a kind of particularly method and composition of the propagation of rhinovirus and rotavirus of nonenveloped virus of controlling especially; Through after the dermal administration composition; Control is present on the application on human skin virus and Sustainable Control virus about 4 or more hours effectively, and up to about 8 hours.
Of the present invention these be in following proposition with other new aspects and benefit, be not limited to the detailed description of preferred embodiment.
Detailed description of preferred embodiments
The personal care product who mixes active antimicrobial is for many years known.Because antimicrobial personal care product's introducing proposes a lot of requirements, such product provides anti-microbial properties.In order to reach the most effective, antimicrobial compositions should provide high log to reduce in short as far as possible time of contact for the wide spectrum organism.Ideally, composition also should inactivation of viruses.
Like current preparation, the soap composition of most coml liquid antibiotic provides difference to MIN fungicidal effectiveness, the i.e. speed of sterilization.These compositions can not be controlled virus effectively.
The alcohol that antimicrobial hand disinfectant composition does not contain surfactant usually and depends on high concentration is controlled bacterium.Therefore the alcohol evaporation can not provide lasting bacterial control.Alcohols can also drying and chafe.
Most of current products lack effectiveness especially for Gram-negative bacteria such as Escherichia coli, and this is special care for human health.Yet, have extra high broad-spectrum antiseptic and render a service the composition existence, as recording through quick sterilization (that is, time kill), this is to be different from lasting sterilization.These products also lack enough antiviral activities.
With the previous alcohol that mixes percentage promptly 40% or the composition of more multiple amount compare, this antimicrobial compositions provides fabulous broad-spectrum antiviral and anti-bacterial effectiveness, has improved antiviral efficacy significantly.The basis that this improvement is renderd a service is to find, the alcohol of sterilization and organic acid and particularly having is lower than the organic acid combination of about 1 log P, improved antiviral efficacy in essence, reaches (b) pH on the surface after the surface applied said composition.
The alcohol of sterilization and have be lower than 1 log P the organic acid synergy with the control nonenveloped virus.The alcohol of sterilization and have 1 or the organic acid synergy of bigger log P to improve antibacterial efficacy in fact.Have first organic acid that is lower than 1 log P and have 1 or second organic acid combination of bigger log P, add the alcohol of sterilization, in the control of nonenveloped virus and gram-positive bacteria and Gram-negative bacteria, collaborative raising is provided.
Although contain the composition of antimicrobial such as triclosan, proving has quick and effective antibacterial activity to gram-positive bacteria and Gram-negative bacteria, and the control of virus is inadequate.In a large amount of transmissions of disease of control, the virus control on skin or the inanimate surfaces is very important.
For example, rhinovirus is to be the relevant most important microorganism of the acute respiratory disease of " flu " with mentioning.Other viruses also be the symptom that suppresses to cause " flu ", but rhinovirus are the flu that causes bigger quantity in theory like parainfluenza virus, Respiratory Syncytial Virus(RSV) (RSV), enterovirus and coronavirus.Rhinovirus still is the most rambunctious in causing the virus of flu, and has in hard desiccated surface more than 4 days ability of surviving.In addition, when being exposed to 70 % ethanolic solutions, most virus is inactivation.Yet, still keep vigor when rhinovirus is exposed to ethanol.
Because rhinovirus is the main known reason that causes flu, the composition that importantly has antiviral activity is effective for rhinovirus.Although be familiar with rhinoviral molecular biology at present, find to prevent the effective ways of the flu that rhinovirus causes, come to nothing and prevent that virus from spreading to the experimenter who does not infect.
As everyone knows, iodine is potent antiviral agent, and lasting rhinovirus activity is provided on skin.Inducing with natural flu experimentally propagated in the research, uses the experimenter of iodine product to use the experimenter of placebo to have flu significantly still less.This shows, iodine is time expand effectively when the propagation of the rhinoviral infection of blocking-up.Therefore, the Products Development that transmits immediately with lasting antiviral activity will be to reduce the incidence of disease of flu effectively.Likewise, the composition that demonstrates antiviral activity of surface use will be to effectively prevent and/or treat by other nonenveloped viruses to comprise the disease that the virus of acid labile causes.
Rotavirus also is a virus nonencapsulated, double shells, and it is stable in environment is.Rotavirus infection is gastral infection, is cacatory common cause among the children, has only just caused the hospitalization that surpasses 50,000 examples every year in the U.S..It is the special problem of sealing group that rhinovirus is infected, like child care facility, gerontology facility, family field children's hospital in one's power.
Transmitting the modal pattern of rotavirus is the person-to-person propagation of hand through polluting, can also be but transmit through the water or the food of ingesting and polluting, or take place through surfaces contaminated.Then, rotavirus is through getting into human body with contacting of oral area.
Be known that cleaning hand and crust with soap and/or other cleaning agents is to kill dead rotavirus not, still helps to prevent its propagation.In the U.S., oral Rotavirus Vaccine has ratified to be used for children, but because serious adverse side effect is not recommended its use.Do not go to remove rotavirus or its propagation because there are other valid approach;, the group of these sealings works in providing those of messes in particular for children; Be current effective, must observe strict hygiene custom to help to reduce the propagation of rotavirus.The antiviral efficacy that in the deactivation rotavirus, has enhancing comprises the improved composition of lasting antiviral efficacy, with the propagation that further reduces rotavirus infection.
Killing the virus, refer to can deactivation or elimination virus." lasting antiviral efficacy " or " the lasting antiviral activity " of As used herein on lived surface (for example are meant; Skin) or stay residual on the inanimate surfaces or give environment, the time of the prolongation after using provides significant antiviral activity.Composition of the present invention provides lasting antiviral efficacy; The virus such as rhinovirus and the rotavirus serotype that promptly comprise acid labile for nonenveloped virus; Contact preferably at least 3 log minimizing within 30 seconds with said composition, be more preferably 4 log minimizing.With after the composition contact, keep antiviral activity at least about 0.5 hour, preferably at least about 1 hour, more preferably at least about 2 hours, at least about 3 hours, or at least about 4 hours.In some embodiment preferred, after with the composition contact, antiviral activity is to keep about 6-about 8 hours.The methodology of measuring permanent disease-resistant toxic effect power below has been discussed.
Antimicrobial compositions of the present invention is highly effective in the quick and lasting control that the quick of bacterium and wide spectrum control, nonenveloped virus are provided.The height effective composition contains the organic acid of the pure and mild effective dose of killing the virus of sterilization.
Sterilization pure and mild has the organic acid synergy that is lower than 1 the log P nonenveloped virus with the control wide spectrum.Sterilization pure and mild have 1 or the organic acid synergy of bigger log P with the bacterium of control wide spectrum.Comprise have first organic acid that is lower than 1 log P with have 1 or the second organic acid composition synergy of bigger log P with the nonenveloped virus of control wide spectrum and the gram-positive bacteria and the Gram-negative bacteria of wide spectrum.
Composition is wonderful gentleness for skin, and for the not corrosion of abiotic surface.Therefore, the gentleness and the effective composition of solution bacterium and viral control problem are provided for the consumer.
Present composition provides effective and lasting deactivation nonenveloped virus.Nonenveloped virus includes, but are not limited to adenovirus, cauliflower mosaic virus group, papovavirus, phycodnavirus, Circovirus, parvovirus group, birnavirus, rotovirus (comprising rotavirus gastroenteritis), astrovirus, Calicivirus (comprising norwalk virus), marmor upsilon group (potyvirus) and picornavirus (comprising rhinovirus, polyovirus and hepatitis a virus).
Antimicrobial compositions of the present invention in family's clean applications (for example; Crust such as floor, work top, bucket, plate and soft cloth material such as clothes), personal care applications (for example; Washing lotion, shower gels, soap, shampoo and rag); And be highly effective in industry and the hospital application (for example, the sterilization of apparatus, medical equipment and gloves).This composition effectively and is apace sterilized and is infected or surfaces contaminated by Gram-negative bacteria, gram-positive bacteria and nonenveloped virus (for example, rhinovirus and rotavirus).This composition also provides lasting antiviral efficacy.
Composition can be used in external and the body.External refer in abiotic article or on, desirably is on inanimate objects especially with crust or pressure release surface, said surface is the place that is positioned at or is used to prevent virus disseminating, the most especially on the object of staff contact.Be meant in the body in lived object or on, particularly on mammal skin, especially on hand.
Like following unrestriced embodiment explanation, antimicrobial compositions of the present invention comprises: (a) alcohol of the sterilization of about 75% weight of about 25%-, (b) the kill the virus organic acid of effective dose reaches (c) water.The said composition composition has and is lower than about 5 pH.In preferred embodiments, said composition contains optional gelling agent.
After 30 seconds contact, composition has shown that to gram-positive bacteria about 2 log reduces.After 30 seconds contact, composition has shown that to Gram-negative bacteria about 2.5 log reduces.After 30 seconds contact; Composition comprises that to nonenveloped virus virus such as the rhinovirus of acid labile and rotavirus serotype have shown that further about 5 log reduces; And the virus of these acid labile having been shown that at least 3 log reduces after about 5 hours of the contact, the virus to these acid labile after about 8 hours of the about 6-of contact has shown at least 2 log minimizing.Composition also is gentle, there is no need to clean or wipe composition from skin.
According to the present invention, this antimicrobial compositions can further contain after this disclosed other composition such as hydrotrote, polyhydroxyl solvents, gelling agent, pH regulator agent, vitamin, pigment, skin conditioning agent and aromatic.Composition be do not contain the cleansing surfactants of have a mind to adding such as anion surfactant and active antimicrobial agent such as phenol with quaternary ammonium antimicrobial.
Following composition is present in the antimicrobial compositions of the present invention.
A. The alcohol of sterilization
Antimicrobial compositions of the present invention contains the alcohol of the sterilization of about 75% weight of the 25%-that has an appointment.The preferred embodiment of the invention contains the alcohol of the sterilization of about 75% weight of the 30%-that has an appointment.Most preferred embodiment contains the alcohol of the sterilization of about 70% weight of the 30%-that has an appointment.
" alcohol of sterilization " as used herein is the alcohol of water soluble, contains 1-6 carbon atom.The alcohol of sterilization includes, but are not limited to methyl alcohol, ethanol, propyl alcohol and isopropyl alcohol.
B. Organic acid
The organic acid that antimicrobial compositions of the present invention also contains capacity with control and deactivation with virus on the antimicrobial compositions contact surface and bacterium.The alcohol synergy of organic acid and sterilization lasting virus control so that quick control nonenveloped virus and/or bacterium to be provided.
Especially, organic acid is to be present in the composition with enough amounts, so that the pH that life or abiotic surface are arranged of composition contact is low to moderate the degree that obtains lasting virus control.Obtain the control of this lasting virus, be with composition whether from the contact surface flush away or to stay the surface that contacts irrelevant.Organic acid keeps in composition that part is undissolved at least, when composition dilutes or application or be still that kind when cleaning.
When being applied to surface as people's skin, to be enough low control so that obtain lasting virus the pH on surface.In preferred embodiments, the organic acid of residual quantity remains on the skin, even after rinse step, so that give lasting virus control.Yet even organic acid is clean fully basically from the surface, surface p H has been enough low to give virus control at least 0.5 hour.
Typically, with respect to composition weight meter, organic acid is included in the said composition with the amount of about 0.05%-about 6%, preferably about 0.1%-about 5%.In order to realize whole benefit of the present invention, organic acid is with respect to composition weight meter, is that the amount with about 0.15%-about 4% exists.The organic acid amount is relevant with the characteristic of used organic acid kind and used acid.
The organic acid that is included in this antimicrobial compositions does not preferably penetrate the surface that it is used, and is for example opposite with transdermal, stays skin surface.Therefore, the preferably hydrophobic organic acid of organic acid.
In embodiments of the invention, organic acid has and is lower than 1 log P, preferably is lower than 0.75.In order to realize whole benefit of the present invention, organic acid has and is lower than 0.5 log P.In this embodiment, the pure and mild organic acid synergy of sterilization is to provide effectively and virus control enduringly.
In another embodiment, organic acid has 1 or bigger log P, and for example 1-about 100.In this embodiment, the pure and mild organic acid of sterilization is controlled nonenveloped virus effectively, but also synergy is with the bacterium of control wide spectrum.
What envision is; Have first organic acid that is lower than 1 log P with have 1 or second organic acid of bigger logP mix composition of the present invention, the alcohol synergy of first and second organic acids and sterilization is controlled with lasting control and broad spectrum of bacteria that nonenveloped virus is provided.
Term as used herein " log P " is the log that is defined as the water-octanol distribution coefficient under balance and 25 ℃, i.e. P w/ P oThe log of ratio, wherein P wBe organic acid concentration in the water, P oBe organic acid concentration in the octanol.Water-octanol coefficient can pass through U.S.EnvironmentalProtection Agency Procedure, and " OPPTS 830.7560 Partition Coefficient (n-Octanol/Water), Generator Column Method " (1996) are measured.
Dissolve, promptly under 25 ℃, have the water solubility of 0.5wt% at least.
Organic acid can comprise hydrophobic monocarboxylic acid; Polybasic carboxylic acid; Acid or its mixture with polymerization of a plurality of carboxyls, phosphate radical, sulfonate radical and/or sulfate radical part.Except acidic moiety, organic acid can also contain other parts for example hydroxyl and/or amino.In addition, organic acid anhydride can be used in the composition of the present invention as organic acid.
In one embodiment, organic acid comprises and has RCO 2The monocarboxylic acid of H structure, wherein R is C 1-6Alkyl, hydroxyl C 1-6Alkyl, halo C 1-6Alkyl, phenyl or substituted phenyl.Alkyl can use phenyl and/or phenoxy group to replace, and these phenyl and phenoxy group can be substituted or unsubstituted.
The non-restrictive example of the monocarboxylic acid that the present invention is used is acetate, propionic acid, glycolic acid, lactic acid, benzoic acid, phenylacetic acid, phenoxy acetic acid, zimanic acid; 2-, 3-or 4-hydroxybenzoic acid, anilic acid; Adjacent-,-or right-chlorobenzene acetic acid, adjacent-,-or right-chlorophenoxyacetic acid and composition thereof.Substituted in addition benzoic acid is to be disclosed in U.S. Patent number 6,294,186, is hereby incorporated by.Substituted benzoic instance comprises; But be not limited to salicylic acid, 2-nitrobenzoic acid, thiosalicylic acid, 2,6-dihydroxy-benzoic acid, 5-nitro-salicylic acid, 5 bromosalicylic acid, 5-iodo-salicylic acid, 5-fluorosalicylic acid, 3-chloro-salicylic acid, 4-chloro-salicylic acid and 5-chloro-salicylic acid.
In another embodiment, organic acid contains polybasic carboxylic acid.Polybasic carboxylic acid contains at least 2, nearly 4 hydroxy-acid groups.Polybasic carboxylic acid can also contain hydroxyl or amino except substituted and unsubstituted phenyl.
The limiting examples of the used polybasic carboxylic acid of the present invention comprises malonic acid, succinic acid, glutaric acid, adipic acid, terephthalic acid (TPA), phthalic acid, pimelic acid, suberic acid, azelaic acid, decanedioic acid, fumaric acid, maleic acid, tartaric acid, malic acid, citric acid, maleic acid, aconitic acid and composition thereof.
Polybasic carboxylic acid and monocarboxylic acid anhydrides still are the used organic acid of the present invention.Preferred acid anhydrides is the acid anhydrides of polybasic carboxylic acid, for example phthalic anhydride.At least a portion of acid anhydrides is hydrolyzed into carboxylic acid, because the pH of composition.What envision is that therefore acid anhydrides can help the antiviral activity that provides lasting in the slowly hydrolysis of the surface of composition contact.
In the 3rd embodiment, organic acid contains the carboxylic acid of polymerization, the phosphoric acid of the sulfonic acid of polymerization, Sulfated polymer, polymerization or its mixture.The acid of polymerization (polymeric acid) has about 500g/mol-10, and 000, the molecular weight of 000g/mol comprises homopolymers, copolymer and composition thereof.The acid of polymerization preferably can form firm film from the teeth outwards, has the glass transition temperature T that is less than 25 ℃ g, preferably be less than 20 ℃, be more preferably and be less than about 15 ℃.Glass transition temperature is amorphous substance such as polymer, changes the temperature of plastic state from fragility, vitreous state.The T of polymer gUsing standard technique by those skilled in the art is easy to measure.
The acid of polymerization is uncrosslinked or only is that very the lower bound degree is crosslinked.The acid of polymerization is normally made by the undersaturated monomer with at least one hydrophilic segment such as carboxyl, carboxylic acid anhydride, sulfonic acid and sulfuric acid of vinylation.The acid of polymerization can contain comonomer such as styrene or alkene, with the hydrophobicity of the acid that increases polymerization.
The instance that is used to prepare the organic acid monomer of polymerization includes, but are not limited to:
(a) contain the carboxyl of monomer; The undersaturated monobasic of for example single ethene (monoethylenically)-or polybasic carboxylic acid is like acrylic acid, methacrylic acid, maleic acid, fumaric acid, crotonic acid, sorbic acid, itaconic acid, ethylacrylic acid, α-Lv Bingxisuan, alpha-cyanoacrylate, Beta-methyl acrylic acid (crotonic acid), atropic acid, β-acryloxy propionic, sorbic acid, α-chlorine sorbic acid, angelic acid, cinnamic acid, to chloro-cinnamic acid, β-stearoyl acrylic acid, citraconic acid, mesaconic acid, glutaconate, aconitic acid, tricarboxylic ethene and cinnamic acid;
(b) contain the monomer of carboxylic acid anhydrides, the undersaturated polybasic acid anhydride of single ethene for example, as maleic anhydride with
(c) contain the monomer of sulfonic acid group, for example aliphatic or aromatic vinyl sulfonic acid such as vinyl sulfonic acid, allyl sulphonic acid, vinyl toluene sulfonic acid, styrene sulfonic acid, (methyl) acrylic acid thio-ethyl ester, 2-acrylic amino-2-methyl propane sulfonic acid, (methyl) acrylic acid sulfo-propyl diester and 2-hydroxyl-3-(methyl) acryloxy propyl sulfonic acid.
The acid of polymerization can contain other copolymerizable unit, i.e. the undersaturated comonomer of other single ethene, and prior art is known, as long as polymer is actually the monomeric unit that contains acidic-group, promptly at least 10%, preferably at least 25%.In order to realize whole benefit of the present invention, the acid of polymerization contains at least 50%, is more preferably at least 75%, and reaches 100% the monomeric unit that contains acidic-group.The unit of other copolymerizableization for example, can be styrene, alkene, alkyl acrylate or alkyl methacrylate.The acid of polymerization can also be the part neutralization, and it helps the acid of polymerization to disperse to get into composition.Yet the acidic-group of q.s is still unneutralized so that reduce skin pH and give lasting antiviral activity.
The acid of a preferred polymerization is polyacrylic acid, homopolymers or copolymer, the for example copolymer of acrylic acid and alkyl acrylate and/or alkyl methacrylate.The acid of another preferred polymerization is the homopolymers or the copolymer of methacrylic acid.
The acid of the exemplary polymerization that the present invention is used includes, but are not limited to:
Figure 715217DEST_PATH_GSB00000368689200041
In the preferred embodiment of the invention; Organic acid comprises one or more polybasic carboxylic acids; For example any two or three whole mixtures of citric acid, malic acid, tartaric acid or these acid; And the acid that contains the polymerization of a plurality of carboxyls, the for example homopolymers of acrylic acid and methacrylic acid and copolymer.
C. Carrier
The carrier of this antimicrobial compositions contains water.
D. Optional ingredients
Antimicrobial compositions of the present invention can also contain optional member well known to those skilled in the art.The specific optional ingredients and the amount that can be present in composition are after this disclosed.
Optional ingredients is to exist with the function of carrying out its expection and the antimicrobial efficacy that does not influence composition unfriendly with enough amounts, the synergistic effect that the pure and mild organic acid that does not especially have adverse effect to sterilize provides.Optional ingredients is normally about 50% with the 0%-of composition weight meter, and is single or jointly exist.
The kind of optional member includes, but are not limited to the optional ingredients of hydrotrote, polyhydroxyl solvents, gelling agent, pigment, aromatic, pH regulator agent, thickener, viscosity modifier, cleaning agent, skin conditioning agent, emollient, preservative, buffer, antioxidant, chelating agent, opacifier and similar kind well known by persons skilled in the art.
If hydrotrote fully, is that amount with about 0.1%-about 30% exists the amount of preferably about 1%-about 20% in the weight of composition.In order to realize whole benefit of the present invention, composition can contain the hydrotrote of about 15% weight of the 2%-that has an appointment.
Hydrotrote is such compound, and it has the water miscible ability that strengthens other compounds.The hydrotrote that the present invention utilizes lacks surfactant properties, the normally alkylaryl sulfonates of short chain.The particular instance of hydrotrote includes, but are not limited to cumene sodium sulfonate, cumene ichthyodin, ammonium xylene sulfonate, potassium toluene sulfonate, toluenesulfonic acid sodium salt, sodium xylene sulfonate, toluenesulfonic acid and xylene monosulfonic acid.Other useful hydrotrotes comprise and gather sodium naphthalene sulfonate, kayexalate, methyl naphthalene sulfonic acid sodium, sodium camphorsulfonate and disodium succinate.
Polyhydroxyl solvents if exist fully, is that amount with about 0.1%-about 30% exists in the weight of composition, and preferably about 5%-about 30% measures.In order to realize whole benefit of the present invention, polyhydroxyl solvents is that amount with about 10%-about 30% exists in the weight of composition.Opposite with the alcohol of sterilization, if exist fully, the polyhydroxyl solvents minimally helps this composition antimicrobial efficacy.
Term as used herein " polyhydroxyl solvents " is the organic compound of water soluble, and containing 2-6 typical case is 2 or 3 hydroxyls.Term " water soluble " is meant at 25 ℃ of following polyhydroxyl solvents to have the water-soluble of the water of polyhydroxyl solvents/100g of 0.1g at least.Water-soluble for polyhydroxyl solvents does not have the upper limit, and for example, polyhydroxyl solvents and water can mix by all proportions.
Therefore, the term polyhydroxyl solvents comprises glycols, three alcohols and the polyalcohols of water soluble.The instance of hydrogeneous solvent includes, but are not limited to ethylene glycol, propane diols, glycerine, diethylene glycol, DPG, tripropylene glycol, hexylene glycol, butanediol, 1,2,6-hexanetriol, sorbitol, PEG-4 and similar polyol.
The optional ingredients of other particular types comprises inorganic phosphate, sulphate and the carbonate as buffer; EDTA and phosphate as chelating agent; Bronsted lowry acids and bases bronsted lowry as the pH regulator agent.
The instance of the preferred type of optional alkaline pH conditioning agent be ammonium-, single-, two-and three-alkyl amine, single-, two-and three-alkanol amine, the hydroxide class of alkali metal and alkaline earth metal, and composition thereof.Yet, do not limit the characteristic of alkaline pH conditioning agent, can use any alkaline pH conditioning agent known in the art.The specific unrestriced instance of alkaline pH conditioning agent is an ammonium, sodium, potassium and lithium hydroxide, monoethanolamine, triethylamine, isopropanolamine, diethanol amine and triethanolamine.
The instance of the preferred type of acidic ph modifier is an inorganic acids.The limiting examples of inorganic acid is hydrochloric acid, nitric acid, phosphoric acid and sulfuric acid.Do not limit the characteristic of acidic ph modifier, can separately or unite and use any acidic ph modifier known in the art.
Provide the optional alkanolamide of composition thickening power to be, but be not limited to cocoyl MEA, cocoyl diethanol amine, soya-bean oil acyl group diethanol amine, lauroyl diethanolamine, oleoyl monoisopropanolamine, stearyl MEA, myristoyl MEA, lauroyl monoethanolamine, capryl diethanol amine, castor oil acyl group glycol amine, myristoyl diethanol amine, stearyl diethanol amine, oleoyl diethanol amine, butter acyl group diethanol amine, lauroyl monoisopropanolamine, butter acyl group MEA, isostearoyl base diethanol amine, isostearoyl base MEA and composition thereof.Alkanolamide is non-clean Surface activating agent, if fully, with the amount adding of thickener composition.
This antimicrobial compositions can also contain the optional gelling agent of about 5% weight of the 0.01%-that has an appointment, preferably about 3% weight of 0.10%-.In order to realize whole benefit of the present invention, antimicrobial compositions contains the gelling agent of about 2.5% weight of the 0.25%-that has an appointment.Antimicrobial compositions contains the gelling agent of capacity usually so that composition is liquid, gel or the semisolid of thickness, can be easy to be applied to and wipe on skin or other surfaces.Those skilled in the art will know that the kind and the amount of gelling agent used in the composition that compositions desired viscosity or denseness are provided.
Here reaching after this used term " gelling agent " is meant the viscosity that can increase aqueous composition or can be transformed into water base composition gel or semisolid compound.Therefore, gelling agent can be the occurring in nature organic matter, and for example natural gum or synthetic polymer can be the inorganic polymer of occurring in nature perhaps.
As discussed previously, said composition is not contain cleansing surfactants and antimicrobial.Cleansing surfactants and antimicrobial are not deliberately not add this antimicrobial compositions, but weight that can 0%-about 0.5% exists, because the coml form that surfactant can gelling agent exists, help in water, to disperse gelling agent.Surfactant can also exist as the additive of other composition components forms or accessory substance.Antimicrobial can be used as preservative and is present in the composition.
It below is the unrestriced instance that can be used for gelling agent of the present invention.Especially, following compound, organic or inorganic, the water-based part through thickening or the following composition of gelling mainly works:
Gum Arabic, agar, phycocolloid, alginic acid, ammonium alginate, ammonium chloride, ammonium sulfate, amylopectin, Attagel, bentonite, C 9-15Alcohol; Calcium acetate; Calcium alginate; Calcium carrageenan; Calcium chloride; Octanol; Carboxymethyl hydroxyethyl cellulose; Carboxy-methyl hydroxy propyl melon glue; Carrageenan; Cellulose; Cellulose gum; 16/octadecanol; Cetanol; Corn starch; Hard gum; Dextrin; Dibenzylidene sorbitol; Ethene dihydro acyl amine; Ethene two oleamide; Ethene distearyl acid amides; Gelatin; Guar gum; Chlorination cluster bean Hydroxyproyl Trimethyl quaternary ammonium; Hectorite; Hyaluronic acid; Hydrated SiO 2; Hydroxy butyl methyl cellulose; Hydroxyethylcellulose; Hydroxyethyl ethylcellulose; Ethoxy stearyl monoisopropanolamine; Hydroxypropyl cellulose; The hydroxypropyl guar bean gum; Hydroxypropyl methylcellulose; Different cetanol; Isooctadecanol; Karaya; Kelp ashes; Laruyl alcohol; Carob gum; Aluminium-magnesium silicate; Magnesium silicate; Magnesium trisilicate; Methoxy PEG-22/ dodecyl diol copolymer; Methylcellulose; Microcrystalline cellulose; Montmorillonite; Myristyl alcohol; Oat meal; Oleyl alcohol; The palm-kernel oil fatty alcohol; Pectin; PEG-2M; PEG-5M; Polyvinyl alcohol; Potassium alginate; Carrageenan potassium; Potassium chloride; Potassium sulphate; Potato starch; The alginic acid polyethylene glycol; Sensor Chip CM 5 sodium; Carrageenan sodium; Cellulose sodium sulfate; Sodium chloride; The sial sodium alkoxide; Sodium sulphate; Bentonite stearyl dixylyl ammonium; Hectorite stearyl dixylyl ammonium; Stearyl alcohol; Tallow alcohol (tallow alcohol); The TEA-hydrochloride; Tragacanth; Tridecyl alcohol; Silicic acid tromethamine magnalium; Wheat flour; Wheaten starch; Xanthans and composition thereof.
Other limiting examples below the gelling agent mainly works through the water-based part of thickener composition:
Abienol, acrylinoleic acid 、 behenic acid aluminium, aluminium octoate, dilinoleic acid aluminium, aluminium distearate, isostearic acid aluminium/Aluminum trilaurate/aluminum palmitate or aluminum stearate, isostearic acid aluminium/aluminium myristate, isostearic acid aluminium/aluminum palmitate, isostearic acid aluminium/aluminum stearate, lanoceric acid aluminium, aluminium myristate/aluminum palmitate, aluminum stearate, aluminium distearate, Aluminium Tristearate Micronized sterile aluminium, beeswax, mountain Yu acid amides, docosyl alcohol, butadiene/acrylonitrile copolymer, C 29-70Acid behenic acid calcium; Calcium stearate; Candelila wax; Cured palm; Paraffin; Cholesterol; The hydroxy stearic acid cholesterol ester; Lauric alcohol; Copal; Stearic acid malic acid diglycerol mixed ester; The dihydro abienol; Dimethyl lauramide oleate; Dodecyl diacid/16/octadecanol/diol copolymer; Erucyl amide (erucamide); Ethyl cellulose; Hydroxy stearic acid glyceryl triacetyl ester; Castor oil acid glyceryl triacetyl ester; Er Chun Er behenic acid ester; The glycol dicaprylate; The glycol distearate; The hexylene glycol distearate; Hydrogenation C 6-14Olefin polymer, rilanit special, hydrogenated cottonseed oil, hydrogenated lard, hydrogenation pilchardine, hydrogenated palm kernel oil fat glycerides, hydrogenated palm kernel oil fat oil, HPO, Parleam, oil with hydrogenated soybean, hydrogenated fat acid amides, hydrogenated tallow glyceride, hydrogenated vegetable glyceride, hydrogenated vegetable glyceride type, hydrogenated vegetable oil, hydroxypropyl cellulose, isobutene/isoprene copolymer, the different cetyl stearoyl of stearic acid ester, Japan tallow, jojoba wax, lanolin alcohol, lauramide, dehydroabietic acid methyl esters, hydrogenated methyl rosinate, methyl abietate, methyl styrene/vinyl toluene copolymer, microwax, montanic acid wax, montan wax, myristyl eicosyl alcohol, myristyl stearyl alcohol, vaccenic acid/copolymer-maleic anhydride, stearic acid octyl group dodecyl stearoyl ester, oleamide, oleostearin, ouricury wax, oxidic polyethylene, ceresine, palm-kernel oil fatty alcohol, paraffin, pentaerythrite hydrogenated rosin acid esters, pentaerythritol abietate, pentaerythrite four rosin esters, season penta tetrol, four behenic acid esters, pentaerythrite four caprylates, pentaerythrite four oleates, pentaerythritol tetrastearate, phthalic anhydride/glycerine/capric acid glycidyl ester copolymer, phthalic anhydride/1; 2; 4 benzenetricarboxylic anhydrides/glycol copolymer, gather cinene, polyethylene, polyisobutene, polyisoprene, polyvinylbutyral, polyethylene laurate, two sad propylene glycol esters, two coconut oil propylene glycol esters, two different n-nonanoic acid propylene glycol esters, two lauric acid propylene glycol esters, two n-nonanoic acid propylene glycol esters, distearyl acid propylene glycol ester, heneicosoic acid propylene glycol ester, PVP/ eicosylene copolymer, PVP/ hexadecylene copolymer, rice bran wax, bentonite stearyl dixylyl ammonium, hectorite stearyl dixylyl ammonium, stearmide, stearyl diethanol amine-distearate, stearyl dihydroxy isobutylamine-stearate, stearyl MEA-stearate, stearone, stearyl alcohol, stearoyl erucyl amide, stearic acid stearoyl ester, stearic acid stearoyl stearyl ester, synthetic bees wax, synthetic wax, trihydroxy tristearin, three isononyl alcohols, three different tristearin, three linseed oil acid, three isostearoyl esters, laurin, three linoleic acid, trilinolein phosphoramide, myristin, glycerol trioleate, tripalmitin, glyceryl tristearate, zinc laurate, Zinc tetradecanoate, zinc neodecanoate, zinc abietate, zinc stearate and composition thereof at polybutene, polypenthylene terephthalate.
The used exemplary gelling agent of the present invention includes, but are not limited to:
Polyethylene glycol & propane diols & water (ACULYN?44)
Acrylated dimethyl ammonium tartrate/VP copolymer (ARISTOFLEX?AVC)
Ying Zhisuanganyouzhi &PEG100 stearate (ARLACEL?165)
Polyethylene (21) stearoyl ether (BRIJ?72)
Polyoxyethylene (21) stearoyl ether (BRIJ?721)
Silica (CAB-O-SIL)
Polyquaternium?10 (CELQUAT?CS23?OM)
Cetanol ?
16/octadecanol &, 16/octodecyl alcohol polyoxyethylene (20) ether (COSMOWAX?P)
16/octadecanol & DCP & 16/octodecyl alcohol polyoxyethylene (10) ether phosphate (CRODAFOS?CES)
16/octodecyl alcohol polyoxyethylene (20) ether phosphate &, 16/octadecanol & DCP (CRODAFOS CS-20 acid)
16/octadecanol &, 16/octodecyl alcohol polyoxyethylene (20) ether (EMULGADE?NI?1000)
Sodium silicate magnesium (LAPONITE?XLG)
Cetanol & stearyl alcohol & stearyl dixylyl ammonium chloride & dimethyl stearylamine & lactic acid (MACKADET?CBC)
The stearic aminopropyl dimethylamine of 16/octadecanol stearoyl amido propyl-dimethyl benzyl ammonium chloride (MACKERNIUM?Essential)
The stearyl dimethyl benzyl ammonium chloride (MACKERNIUM?SDC85)
The stearic aminopropyl dimethylamine of 16/octadecanol stearoyl amido propyl-dimethyl benzyl ammonium chloride siloxanes Quaternium 16 (MACKERNIUM?Ultra)
16/Shi Bachun &Cetearyl glucoside (MONTANOV?68EC)
Hydroxyethylcellulose (NATROSOL?250HHR?CS)
Polyquaternium-37& mineral oil & trialkyl polyoxyethylene (6) ether (SALCARE?SC?95)
[0137]
Polyquaternium-32& Kuang Wuyou & Trialkyl polyoxyethylene (6) ether (SALCARE SC 96)
Stearic acid
The cetyl hydroxyethylcellulose (NATROSOL Plus 330CS)
Polyvinyl alcohol, PVP-K30, propane diols
Stearic acid, docosyl alcohol, tristerin, lecithin, C12-16 alcohols, palmitic acid (PROLIPID 141)
Beeswax (beeswax of saponification)
Beeswax (synthetic beeswax)
Water, beeswax, sesame oil, lecithin, methyl hydroxybenzoate (peak breast)
Polyquaternium 10 (CELQUAT SC240C)
PAA/Acrylo dimethyl sodium taurocholate Gong Juwu & Yi Shiliuwan & Polyoxyethylene sorbitan monoleate (SIMULGEL EG)
Polyquaternium 44 (LUVIQUAT Care)
E. pH
The pH of this antimicrobial compositions is lower than approximately 5, preferably is lower than about 4.5.In order to realize whole benefit of the present invention, pH is lower than about 4.Usually, the pH of said composition is that about 2-is about 5, preferably about 2.5-about 4.5.
The pH of composition is enough low, so that the organic acid of at least a portion is a protonated form.Organic acid has the ability of the pH that reduces surface p H such as skin so, so that effective virus control, not chafe to be provided.Organic acid also is deposited on the skin, withstands the removing of cleaning, so that lasting antiviral efficacy to be provided.
For the new and unexpected result who proves that antimicrobial compositions of the present invention provides, the embodiment below the preparation has measured Combination Control gram-positive bacteria and Gram-negative bacteria and has controlled rhinoviral ability.Below the percentage by weight listed of each embodiment represent actual or effective weight of each component in the composition.According to it will be apparent to those skilled in the art that with the following stated, make composition through blending constituent.
Following method is to be used for preparation and test embodiment:
A) mensuration of the quick sterilization of antimicrobial product (Time kill) ability.The activity of bactericidal composition is to record through method for disinfection, and the biological survival rate of attack that is exposed to antibiotic subject composition whereby is to confirm as the function of time.In this test, under specific temperature, make the aliquot known specific time cycle of test flora of composition contact of dilution.When the end of time cycle, make subject composition invalid, this has just stopped the antibacterial activity of composition.Calculate the percentage of initial flora or optionally log minimizing.
Usually, method for disinfection is known to those skilled in the art.
Composition can reach under any concentration of 100% and test.The selection of used concentration is that researcher at one's discretion handles, and the concentration that is fit to is that those skilled in the art are easy to confirm.For example, the normally test under 50% dilution factor of the sample of thickness, on the contrary the sample of thickness not need not to dilute.The sample of test is positioned in the aseptic 250ml beaker of equipment magnetic stirring bar, and if desired, sample size is to add to 100ml with aseptic deionized water.All tests are carrying out in triplicate, and synthesis result writes down average log and reduces.
The selection in cycle time of contact also is that the researcher handles at one's discretion.Can select any cycle time of contact.Be 15 seconds-5 minutes common time of contact, and 30 seconds-1 minute is typical time of contact.The contact temperature also can any temperature.Normally about 25 degrees centigrade room temperature.
Bacterial suspension or test inoculum are to make through the growth of bacterial cultures in any suitable solid culture medium (for example, agar).Bacterial flora is with aseptic physiological saline flush away from the agar then, and the suspension of regulating bacterial flora is to about 10 8Colony forming unit/milliliter (cfu/ml).
Following table has been listed used test bacterial cultures and has been comprised that bacteria name, ATCC (American Type Culture Collection) are identified number and the abbreviation of the title of used biology after this.Aurococcus is a gram-positive bacteria, and Escherichia coli, pneumobacillus and hog cholera sramana (family name) bacterium are Gram-negative bacterias.
Biological name ?ATCC# Abbreviation
Aurococcus ?6538 S.aureus
Escherichia coli ?11229 E.coli
Pneumobacillus ?10031 K.pneum
Hog cholera sramana (family name) bacterium ?10708 S.choler
The beaker that contains subject composition is positioned over (if expectation stationary temperature) in the water-bath, or is placed on the magnetic stirring apparatus (if around the expectation laboratory temperature).Sample is inoculated the test bacterial suspension of 1.0ml then.Inoculum and subject composition stir preset time of contact.Expire when time of contact, subject composition/bacterial mixture of 1.0ml shifts the into neutralizer solution of 9.0ml.Make decade be diluted to denumerable scope then.For different biologies, dilution factor can be different.Selected dilution factor covers (TSA+ is the trypticase soya agar that contains lecithin and polyoxyethylene sorbitan monoleate) on the TSA+ plate in triplicate.Plank was hatched 24 ± 2 hours then, and colony count survivor number and calculated percentage or log reduce.Contrast counting (contrast number) is to confirm that through carrying out above-mentioned step exception is to use deionized water to replace subject composition.Through the standard microorganism method, the plate counting converts contrast and sample cfu/ml respectively to.
The Log minimizing is to use computes:
Log minimizing=log 10(contrast number)-log 10(test specimen survivor)
Following table reduces with the log minimizing percentage of flora and connects.
% reduces Log reduces
90 1
99 2
99.9 3
99.99 4
99.999 5
B) antiviral residual potency test (Residual Efficacy Test)
Reference: S.A.Sattar; Standard Test Method for Determining the Virus-Eliminating Effectiveness of Liquid Hygienic Handwash Agents Usingthe Finger-pads of Adult Volunteers, Annual Book of ASTMStandards.Designation E1838-96 is incorporated herein by reference at this in full, and is related to " Sattar I "; People such as S.A.Sattar, Chemical Disinfection to InterruptTransfer of Rhinovirus Type 14 from Environmental Surfaces toHands, Applied and Environmental Microbiology; The 59th volume; The 5th phase, in May, 1993,1579-1585 page or leaf; Be incorporated herein by reference in full at this, be related to " SattarII ".
Measuring the used method of antiviral index of the present invention is the improvement of the test of the viricidal activity that is used for liquid hand cleanser (product of needs flushing after using) described in the Sattar I.This method changes in this case, so that the authentic data of staying product on the skin to be provided.
It is directly to be sent on the skin that the improvement of Sattar I comprises according to following product, according to the virus inoculation of following thumb pad, uses ten circulations (ten-cycle) flushing to reclaim virus.The skin site of inoculation is to handle and should fully sterilize in the zone with 70% dilution ethanol water then.
Operation:
Test in ten minutes:
The initial usefulness of experimenter (each test products 5 people) the not soap of pastille is washed one's hands, and cleans hand, makes hand dry.
Then, hand is also air-dry with 70% Ethanol Treatment.
Test products (1.0ml) is applied to hand, except thumb, makes its drying.
Use product 10 minutes (± 30 seconds) afterwards, use micropipet rhinovirus 14 suspensions (ATCC VR-284, about 1 * 10 of 10 μ l 6PFU (plaque forming unit)/ml) is locally applied to the different loci on hand within the skin surface of the appointment that is known as thumb pad.At this moment, rhinoviral solution also is applied to untreated thumb in an identical manner.
After 7-10 minute whole dry up the cycle; From eluent (salting liquid (EBSS) that contain the Earle ' s balance of 25% fetal bovine serum (FBS)+1%pen-strep-glutamate) the wash-out virus of each different skin site with 1ml, each site is washed 10 times then.
The skin site of inoculation is again through cleaning sterilization fully with 70% ethanol.Use standard technique promptly, plaque is measured or TCID 50(tissue culture infective dose) measured virus titer.
Test in 1 hour:
Make the experimenter between the time point of 1 hour and 3 hours, continue normal movable (exception is to inhale hand).After 1 hour, on the site of thumb pad appointment, accurately use and wash-out rhinovirus suspension according to test in above 10 minutes is described.
Embodiment 1
Composition below the preparation.
Sample Composition (wt%)
A The water that contains 62% ethanol
B The water that contains 30% ethanol
C Contain 2% salicylic 62% ethanol/water
D Contain 2% salicylic 30% ethanol/water
E Contain 2% salicylic DPG/water
[0172]In the sterilization suspension test, the test sample is for the antiviral activity of rhinovirus IA and rotavirus Wa.Following table has been summed up the result of test.
Figure G05847794620070808D000261
This embodiment has explained sterilization pure and mildly has the organic acid combination that is lower than 1 log P the synergistic corrosion virus effect is provided.Sample A and B show that the alcohol of independent sterilization does not provide acceptable virus control.Sample E shows, is dissolved in the virus serotype that salicylic acid does not have complete inactivation to test in DPG and the water.Yet, sample C and D, it is a composition of the present invention, has eliminated the virus serotype of test fully.
Embodiment 2
Antiviral composition below the preparation, can reduce pH, and be applied to people volunteer's thumb pad:
Figure G05847794620070808D000262
1)Acrylic acid ester/acrylic acid C 10-30The Arrcostab interpretation;
2)The preservative that contains propane diols, diazonium ureine, methyl p-hydroxybenzoate and propylben.
The pH of sample 2 is 3.1.
In test, sample 2 is applied to the thumb pad of all fingers of 8 volunteers, except thumb.Thumb is a control site.The volunteer is divided into 4 groups, every group of 2 people.Then, on all thumb pads of every hand, each organize I-IV at preset time with the rhinovirus attack of tiring, render a service with the time correlation of confirmed test composition.Be suitable for each group this moment, also measure the time course of the skin pH of thumb pad with the skin pH of definite response test composition.Each predetermined test period that rhinovirus is attacked and skin pH measures of organizing I-IV is respectively 5 minutes, 1 hour, 2 hours and 4 hours.Average log (rhinovirus tire inoculum), mean skin pH and average log (rhinovirus of recovery is tired) that following table has been summarized volunteer's test thumb pad in the research divide into groups to form.
Group Initial skin pH (on average) after using Skin pH (on average) during test Log (inoculum is tired) (on average) Log (tiring of recovery) (on average)
I 3.0 3.0 3.9 0.23
II 2.8 3.4 4.0 0.23
III 3.0 3.8 3.8 0.23
IV 3.0 3.8 4.3 0.23
The data (that is, different time points) of each group show that it is to be lower than 1 virion that average rhinovirus of reclaiming is tired, or is lower than the detectability of experiment.Effectiveness after this data declaration the present invention 4 hours, and further proof is lower than about 4 skin pH to eliminate virus attack is in full force and effect.
Embodiment 3
The thumb pad of test experimenter's cleaning is with following compositions-treated.Baseline skin pH reading is to be recorded by the thumb pad before the compositions-treated.Carry out skin pH on the thumb pad after the composition dries immediately and measure, after 4 hours, carry out skin pH then again and measure.
Sample Composition (wt%) Mean skin Ph (T=0) Mean skin Ph (T=4 hour) Virus Log 10 reduces The viral % that hand contains
A 2% citric acid, 2% malic acid, 62%ETOH, 1.25 % hydroxyethylcelluloses 2.81 3.23 ＞3log 10 0
B 2% citric acid, 2% tartaric acid, 62%ETOH, 1.25 % hydroxyethylcelluloses 2.64 3.03 ＞3log 10 0
C 2% malic acid, 2% tartaric acid, 62%ETOH, 1.25 % hydroxyethylcelluloses 2.66 2.94 ＞3log 10 0
D 62% ethanol, 1.25% hydroxyethylcellulose 5.53 5.13 ＜0.5log 10 100
E 2% citric acid, 2% malic acid, 70%ETOH, 1% polyacrylic acid 2.90 3.72 ＞3log 10 0
F 70%ETOH, 1% polyacrylic acid 4.80 5.16 2.0log 10 100
G 70%ETOH, 1.25% hydroxyethylcellulose 5.3 5.25 ＜0.5log 10 100
1)ETOH is an ethanol
After thumb pad was handled 4 hours with sample A-G, rhinovirus 39 was tiring 1.3 * 10 3Be applied to thumb pad under the pfu (plaque forming unit).Virus on thumb pad dry 10 minutes, thumb pad reclaims meat soup with the virus that contains 75%EBSS and contain the antibiotic 25%FBS of IX and cleans then.Sample reclaims in the meat soup serial dilution and covers on the H1-HeLa cell in virus.Measure according to each plaque and to tire.The rhinovirus 39 of complete inactivation promptly reduces greater than 3 log, is to use the composition that contains acid that comprises citric acid, malic acid and tartaric mixture to realize.
Embodiment 4 antibacterial activities
Figure G05847794620070808D000291
1)Time of contact on the skin.
A.62% ethanol, 2% citric acid, 2% malic acid, 1.25% hydroxyethylcellulose
B.62% ethanol, 2% citric acid, 2% malic acid, 1.25% hydroxyethylcellulose and skin emollient
This embodiment has explained that composition of the present invention also provides fast and broad spectrum antibiotic activity.
Embodiment 5
Test experimenter's cleaning thumb pad uses following compositions-treated.Baseline skin pH reading is to be measured by the thumb pad before the compositions-treated.Carrying out skin pH on the thumb pad after the composition dries immediately measures.
Thumb pad is with after the compositions-treated, and rhinovirus 14 is tiring 1.4 * 10 4Be applied to thumb pad immediately under the pfu (plaque forming unit).Virus on thumb pad dry 10 minutes, thumb pad reclaims meat soup with the virus that contains 75%EBSS and contain the antibiotic 25%FBS of IX and cleans then.Sample reclaims in the meat soup serial dilution and covers on the H1-HeLa cell in virus.Measure according to each plaque and to tire.The rhinovirus 14 of complete inactivation is to obtain with the composition that contains acid, obtains 4log and reduces.
Sample Composition (wt%) PH value of solution 30 seconds viral Log 10 reduces The viral % that hand contains
A 2% citric acid, 2% malic acid, 70%ETOH, 1% polyacrylic acid 3.10 4Log 0
[0200] Embodiment 6
Composition below the preparation is tested the influence for skin pH and antiviral efficacy of organic acid and organic acid admixture.
Sample Composition (wt%) Mean skin pH (T=0) Mean skin pH (T=4 hour) Virus Log 10 reduces
A 4% citric acid in 70% ethanol/water 2.97 3.64 ＞3log 10
B 4% malic acid in 70% ethanol/water 2.91 3.94 ＞3log 10
C 2% citric acid in 70% ethanol/water and 2% malic acid 2.99 3.38 ＞3.log 10
D 4% tartaric acid in 70% ethanol/water 2.56 3.0 ＞3log 10
Test experimenter's cleaning thumb pad is to handle with sample A-D.Baseline skin pH reading is by measuring with the thumb pad before the compositions-treated.Carry out skin pH on the thumb pad after the composition dries immediately and measure, after 2 hours, carry out skin pH again and measure.
All samples A-D suppresses skin pH and is lower than 4, continues 2 hours.The identical acid of using separately (sample A and B), lower pH was kept in the combination of citric acid and malic acid (sample C) at 2 hours.4% tartaric acid composition (sample D) has shown the inhibition bigger to skin pH.
Thumb pad is with after the solution-treated 2 hours, and rhinovirus 39 is tiring 4 * 10 4Be applied to thumb pad under the pfu.Virus on thumb pad dry 10 minutes, thumb pad reclaims meat soup with the virus that contains 75%EBSS and contain the antibiotic 25%FBS of IX and cleans then.Sample reclaims in the meat soup serial dilution and covers on the H1-HeLa cell in virus.Measure according to each plaque and to tire.Obtain the rhinovirus 39 of complete inactivation, the log that produces greater than 3 reduces.
Following embodiment explanation, in the presence of alcohol, acid and particularly acrylate homopolymer or the copolymer of polymerization give antiviral efficacy.The acid of polymerization has low pH and the substantivity good to skin, and it keeps low skin pH effectively along with the time, helps the antiviral efficacy that provides lasting.
In the presence of alcohol, use, prove the synergistic effect that skin pH is reduced based on the polymerizing acrylic acid thing.Yet, in the skin pH that can not keep in time reducing based on the polymerizing acrylic acid thing identical degree extremely that does not have in the presence of the alcohol.Important ground, when the acid and the alcohol of polymerization were united use, skin pH reduced the less composition pH that depends on.The synergistic effect that proves between the acid of polymerization and the alcohol is unexpected, is the new mode of lower skin pH that the antiviral efficacy of expectation is provided.
When being when using based on the polymerizing acrylic acid thing, also proved for fast and the synergistic effect of permanent disease-resistant cytotoxic activity with polyacrylic acid.According to finding, utilize the antiviral efficacy that has strengthened polybasic carboxylic acid together with the acid (for example, about 2% weight of about 0.1%-) of a spot of polymerization of polybasic carboxylic acid such as citric acid, malic acid, tartaric acid and composition thereof.This synergistic effect has reduced the polybasic carboxylic acid concentration in the antiviral composition, does not follow the reduction of antiviral efficacy.This reduction of polybasic carboxylic acid concentration has improved the composition mildness through the stimulation possibility that reduces composition.
Embodiment 7
Containing polyacrylic acid (1%wt) promptly makes 70% ethanol water and water from the composition that Novean Europe obtains ULTREZ 20.Each composition (1.8ml) is applied to test experimenter's thumb, forefinger and middle finger.Measure skin pH reading (baseline) before handling, measure skin pH after finger is dry and after 2 hours.Mean skin pH reading is to be summarised in the following table.
Figure 494954DEST_PATH_GSB00000368689200051
Initial polyacrylic acid suppresses skin pH to about 4.5, and skin pH still is lower than 5 after 2 hours.The composition that contains ethanol suppresses skin pH (4.4) a shade below the composition that does not contain ethanol (4.5).The result has disclosed, when polyacrylic acid uses with ethanol, for the synergistic effect that reduces skin pH.
After above-mentioned compositions-treated thumb pad 2 hours, rhinovirus 39 is applied at 9.8x10 2The thumb pad of handling under the tiring of pfu.Virus on thumb pad dry 10 minutes, thumb pad reclaims meat soup with virus and cleans then.Broth reclaims in the meat soup serial dilution and covers on the H1-HeLa cell in virus.Measure according to each plaque and to tire.Two composition bacterium have reduced virus titer.Yet the composition that contains ethanol has shown bigger a little effectiveness to rhinovirus, through the reduction 1.8log that tires, does not more contain ethanol composition and reduces 1.5log.
Data declaration, polyacrylic acid suppress skin pH and produce antiviral efficacy.Data explain that also polyacrylic acid and ethanol act synergistically and reduces skin pH, therefore rhinovirus are produced bigger effectiveness.
In order to confirm this effectiveness, prepare following 8 compositions, the solution for buffering that wherein contains polyacrylic acid (have and do not have ethanol) is to about pH of 4.5,5.0,5.5 or 6.0.
Sample Composition (wt%) PH value of solution 2 hours mean skin pH Virus Log 10 reduces
A 1%ULTREZ 20/70% ethanol 4.54 4.52 ＞2log 10
B 1%ULTREZ 20/70% ethanol 5.10 4.87 ＞2log 10
C 1%ULTREZ 20/70% ethanol 5.54 4.41 ＞2log 10
D 1%ULTREZ 20/70% ethanol 6.17 4.32 ＞2log 10
E 1％ULTREZ?20 4.57 4.93 ＜1log 10
F 1％ULTREZ?20 5.12 5.46 ＜1log 10
G 1％ULTREZ?20 5.55 5.33 ＜1log 10
H 1％ULTREZ?20 6.32 5.70 ＜1log 10
8 compositions have been test for skin pH and viral effectiveness effect.Each composition (1.8ml) is applied to test experimenter's thumb, forefinger and middle finger.Measure skin pH reading (baseline) before handling, measure skin pH after finger is dry and after 2 hours.
Skin pH data show that polyacrylic acid and ethanol synergy are to suppress skin pH, because with respect to the composition that does not contain ethanol, each composition that contains the ethanol that makes up with polyacrylic acid suppresses skin pH extremely than low value.Contain ethanol and polyacrylic composition and reduce skin pH to 4-5, be independent of pH value of solution.On the contrary, the composition that does not contain ethanol only suppresses skin pH to 5-6, and final skin pH is similar with pH value of solution.
Render a service for the virus of testting above-mentioned composition, rhinovirus 39 is 1.7 * 10 after 2 hours 3Be applied to thumb pad under the tiring of pfu.Dry 10 minutes of virus, wash-out reclaims serial dilution in the meat soup in virus.Sample covers on the H1-HeLa cell, measures virus titer according to each plaque determination method.Contain composition with the ethanol of polyacrylic acid combination and have the virus titer that reduces greater than 2 log, however do not contain ethanol compositions display be less than the virus titer that 1log reduces.Therefore, when reducing skin pH, have synergy between polyacrylic acid and the ethanol, it provides the antiviral efficacy bigger to rhinovirus.
Embodiment 8
Prepare following composition and further specify the antiviral efficacy that polyacrylic acid provides.
Figure DEST_PATH_GSB00000368689200061
1)CRODAFOS CS20 Acid is a Ceteth-20 & Cetaryl Alcohol & DCP; With
2)NATROSOL 250HHR CS is a hydroxy ethyl fiber
Sample A-C (1.8ml) is applied to thumb, forefinger and the middle finger of cleaning hand.Measure skin pH reading (baseline) before handling, measure skin pH reading after finger is dry, after 2 hours, measure skin pH, after 4 hours, measure skin pH for sample C for sample A and B.The mean value of skin pH value is provided in last table.
Contain polyacrylic sample A and reduce skin pH to maximum scope, 2 final skin pH after as a child are pH 4.7.Sample B or sample C fail to reduce skin pH and are lower than pH 5.0.These data show that polyacrylic acid has the skin of inhibition pH and keeps low at least 2 hours ability of skin pH.
Also having test sample A-C renders a service for the virus of rhinovirus 39.About 10 3The virus load of pfu is coated on thumb, forefinger and the middle finger of each test hand, makes its dry 10 minutes.Finger reclaims meat soup with virus and cleans, and the sample serial dilution covers on the H1-HeLa cell.Use plaque to measure and measure virus titer.For sample B and C, 100% hand is to show positive for rhinovirus, and it shows that these compositions do not have to render a service for rhinovirus.On the contrary, sample A has confirmed viral effectiveness, is to find rhinovirus is shown positive because 63% hand is only arranged.
Embodiment 9
Embodiment 7 has confirmed, has synergy between polyacrylic acid and the ethanol, and it produces inhibition and the antiviral efficacy of skin pH.Composition below the preparation is with the effect for antiviral efficacy of the composition of inspection polybasic carboxylic acid admixture and the single polybasic carboxylic acid that makes up with polyacrylic acid and ethanol separately.Preferred antiviral composition contains the organic acid that need prove permanent disease-resistant toxic effect strength at least.
Composition is applied to the thumb pad of cleaning hand.After the time of indicating, about 10 3To 10 4The rhinovirus 39 of pfu is applied to hand, makes its dry 10 minutes.Reclaim meat soup with virus and clean hand, reclaim virus.Sample reclaims in the meat soup in virus then and dilutes, and covers on the H1-HeLa cell.Measure definite virus titer through plaque.The percentage that rhinovirus is shown the hand of the positive is summed up as follows.
Figure DEST_PATH_GSB00000368689200071
The composition that only contains 70% ethanol is invalid as antiviral composition.After 1 hour, citric acid (1%) and malic acid (1%) have been lost effect for rhinovirus, because find that the hand for rhinovirus 100% is positive.On the contrary, when the composition that contains 1% citric acid and 1% malic acid is applied to hand with polyacrylic acid and 70% ethanol, do not detect virus after 4 hours.The combination of single acid (4% citric acid) and polyacrylic acid and ethanol is more weak effect for rhinovirus, because after 1 hour, finds that 91% hand is the positive for rhinovirus.
This data acknowledgement uses polyacrylic acid and ethanol to make the polybasic carboxylic acid of low concentration obtain the antiviral efficacy of expectation.
Embodiment 10
The use of polyacrylic acid and ethanol has suppressed skin pH to the value that is lower than pH value of solution in the composition, confirms like embodiment 7.Whether can be buffered to higher pH value of solution and still provide 4 or be lower than 4 skin pH in order to test the antiviral composition that contains citric acid, malic acid, polyacrylic acid and ethanol to obtain lasting antiviral activity, the composition below the preparation.
Figure DEST_PATH_GSB00000368689200081
Composition (1.8mL) is applied to thumb, forefinger and the middle finger of cleaning hand.Measure skin pH reading (baseline) before handling, measure skin pH after finger is dry and after 4 hours.Average skin pH value as above provides.
The initial skin pH of the skin of handling with sample A-C suppresses to pH2.9-3.6 wherein lower pH value of solution, lower initial skin pH.Yet after 4 hours, the skin pH of all three compositions is about pH 3.7.Consistent with previous embodiment, pH value of solution does not indicate skin pH subsequently.
Still having test sample A-C renders a service for the virus of rhinovirus 39.About 10 3The virus load of pfu is coated on thumb, forefinger and the middle finger of each hand of handling, and makes its dry 10 minutes.Finger reclaims meat soup with virus and cleans, and the sample serial dilution covers on the H1-HeLa cell.Use plaque to measure and measure virus titer.Be not recovered to virus, show that all three sample A-C have antiviral efficacy from any hand.
This data acknowledgement; When citric acid and malic acid are used for composition together with polyacrylic acid and ethanol; The pH of solution can be buffered to higher pH, for example is the safer pH of milder for skin, still has the ability that suppresses skin pH and performance antiviral activity simultaneously.
Antimicrobial compositions of the present invention has the product purpose of multiple reality; Comprise mouthwashes, surgical scrub, body splashes, preservative, disinfectant, hand disinfectant gel, deodorant, dental care additive, and similar personal care product.The composition of type comprises foam compositions such as emulsifiable paste, mousse etc. in addition, and contains composition such as emulsion, washing lotion, emulsifiable paste, the paste etc. of organic and inorganic filler material.Composition further can be used as antimicrobial, is used for the crust for example sink and the workbench thereof of hospital, food service district and meat processing factory.This antimicrobial compositions can be fabricated to the wieldy composition of dilution, or the concentrate that dilutes before use.
Therefore the present invention includes use effective dose antimicrobial cleansing compositions of the present invention on non-skin surface, like the surface (cutting board, plate, jar and pan etc.) of work top, surface, kitchen, food preparation for example, the surface of family; Principal home front yard apparatus is refrigerator, refrigerator, washing machine, automatic dryer, baking box, micro-wave oven and dishwashers for example; Cabinet, wall, floor, bathroom, surface, shower curtain, dustbin and/or collection box etc.
Composition can also mix fabric antimicrobial scouring article are provided.The scouring article can be used for cleaning and sterilization has life or abiotic surface.
In one embodiment of the invention; (a) other individualities that maybe possibly contact by rhinovirus flu to suffer the rhinovirus flu, or (b) be maybe possibly contact by rotavirus infection to suffer other individual people of rotavirus infection to be applied to his or her hand to this antimicrobial compositions.The bacterium of existence on hand and rhinovirus, rotavirus and other the nonencapsulated virions that deactivation exists are on hand killed in this application.The composition of using can or stay on hand it with the back flush away, and lasting antiviral activity is provided.Therefore, nonenveloped virus such as rhinovirus and rotavirus particle are not to be conveyed to the individuality that does not infect through hand adversary's propagation.Use composition amount, access times, and cycle of using will according to the sterilisation level of expectation for example microbial contamination and/or the skin degree of getting dirty change.
This antimicrobial compositions is provided at the benefit that short wide spectrum time of contact kills gram-positive bacteria and Gram-negative bacteria and the control of wide spectrum virus.In view of sterilization skin and inanimate surfaces 15-60 time limit second normally, for the log minimizing of bacterium in fact, short contacting time is important.Composition also gives lasting antiviral activity to the surface of contact.Said composition is effectively at short contacting time, because the synergistic effect that the pure and mild organic acid of sterilization provides.
Significantly, the of the present invention multiple modification that proposes like preceding text and change and can carry out not deviating under its spirit and the scope, so such restriction only should be forced at, and additional claim points out.

Claims (48)

  1. The combinations thing preparation be used for reducing and/or the deactivation mammal skin on the application of antimicrobial compositions of bacterium and virus groups; Comprise; With above-mentioned composition contacting skin 30 seconds, at least 2 the log of aurococcus is reduced obtaining, the log of Escherichia coli at least 2.5 is reduced; Log to nonencapsulated virus at least 4 reduces, and above-mentioned composition contains:
    (a) alcohol of the sterilization of 25%-75% by weight, the alcohol of said sterilization comprises one or more C 1-6Alcohol;
    (b) organic acid of 0.05%-6% by weight, it comprises (i) more than a kind of polybasic carboxylic acid with (ii) have the acid of the polymerization of a plurality of carboxyls, and
    (c) water,
    Wherein said composition has 5 or lower pH in the time of 25 ℃, and said composition reduces skin pH extremely less than 4 after dry on skin,
    Wherein organic acid comprises the polybasic carboxylic acid that contains 2-4 hydroxy-acid group, and randomly contains one or more hydroxyls, amino or both, and the acid of polymerization is selected from phosphoric acid of the sulfonic acid of the carboxylic acid of polymerization, polymerization, Sulfated polymer, polymerization and composition thereof.
  2. 2. the application of claim 1, wherein virus is the virus of acid labile.
  3. 3. the application of claim 2, wherein the virus of acid labile comprises rhinovirus serotype.
  4. 4. the application of claim 1, wherein nonencapsulated virus comprises rotavirus serotype.
  5. 5. the application of claim 1 further comprises the step from skin-cleaning composition.
  6. 6. the application of claim 1, wherein skin has lasting antiviral activity.
  7. 7. the application of claim 1, wherein the amount of alcohol in composition of sterilization is 30%-75% based on composition weight meter.
  8. 8. the application of claim 1, wherein the alcohol of sterilization is to be selected from methyl alcohol, ethanol, isopropyl alcohol, n-butanol, normal propyl alcohol and composition thereof.
  9. 9. the application of claim 1, wherein the organic acid in the composition has and is less than 1 log P.
  10. 10. the application of claim 1, wherein the organic acid in the composition has 1 or bigger log P.
  11. 11. the application of claim 1, wherein organic acid comprises and has first organic acid that is lower than 1 log P and have 1 or second organic acid of bigger log P.
  12. 12. the application of claim 1, wherein polybasic carboxylic acid is selected from malonic acid, succinic acid, glutaric acid, hexanedioic acid, pimelic acid, suberic acid, azelaic acid, decanedioic acid, fumaric acid, maleic acid, tartaric acid, malic acid, maleic acid, citric acid, aconitic acid and composition thereof.
  13. 13. the application of claim 1, wherein organic acid comprises the acid anhydrides of polybasic carboxylic acid.
  14. 14. the application of claim 1, wherein organic acid comprises having 500-10,000, and the acid of the polymerization of 000g/mol molecular weight.
  15. 15. the application of claim 14, polymerized therein acid be water soluble or water dispersible.
  16. 16. the application of claim 14, polymerized therein acid comprises acrylic acid homopolymers or copolymer.
  17. 17. the application of claim 1, wherein polybasic carboxylic acid comprises citric acid, malic acid, tartaric acid and composition thereof, and the carboxylic acid of polymerization comprises the homopolymers or the copolymer of acrylic or methacrylic acid.
  18. 18. the application of claim 17, polymerized therein carboxylic acid comprises acrylic acid homopolymers or copolymer.
  19. 19. the application of claim 1, wherein composition further contains gelling agent.
  20. 20. the application of claim 1, wherein composition has 2 to less than 5 pH.
  21. 21. the application of claim 1, wherein mammal skin is contacting the skin pH that had less than 4 in 4 hours later.
  22. 22. the application of claim 1, wherein composition further comprises the polyhydroxyl solvents that is selected from glycol, triol and composition thereof of 0.1%-30%.
  23. 23. the application of claim 1, wherein composition further comprises the hydrotrote of 0.1%-30% by weight.
  24. 24. the application of claim 1, wherein composition further comprises the gelling agent of 0.1%-3% by weight.
  25. 25. the application of claim 24, wherein gelling agent comprises natural gum, synthetic polymer, clay, oil, wax or its mixture.
  26. 26. the application of claim 24, wherein gelling agent is to be selected from cellulose, cellulose derivatives, guar gum, guar gum derivative, phycocolloid, phycocolloid derivative, water-insoluble C 8-C 20Alcohol, carrageenan, montmorillonitic clay, polyquaternium compound and composition thereof.
  27. 27. the application of claim 1, wherein composition does not contain the surfactant of anion, cation and both sexes.
  28. 28. the application of claim 1, wherein composition does not contain active antimicrobial agent.
  29. 29. the application of claim 1, wherein composition gives at least 3 log minimizing at least after contacting 4 hours for nonenveloped virus.
  30. 30. the application of claim 1, wherein composition gives at least 2 log minimizing at least after contacting 6 hours for nonenveloped virus.
  31. 31. the combinations thing is used for deactivation and/or kills virus and the application of the antimicrobial compositions of bacterium in preparation, comprises that above-mentioned composition comprises to the needs step of the mammal skin local application said composition of processing like this:
    (a) alcohol of the sterilization of 25%-75% by weight, the alcohol of said sterilization comprises one or more C 1-6Alcohol;
    (b) organic acid of 0.05%-6% by weight, it comprises (i) more than a kind of polybasic carboxylic acid with (ii) have the acid of the polymerization of a plurality of carboxyls, and
    (c) water,
    Wherein said composition has 5 or lower pH in the time of 25 ℃, and said composition reduces skin pH extremely less than 4 after dry on skin,
    Wherein organic acid comprises the polybasic carboxylic acid that contains 2-4 hydroxy-acid group, and randomly contains one or more hydroxyls, amino or both, and the acid of polymerization is selected from phosphoric acid of the sulfonic acid of the carboxylic acid of polymerization, polymerization, Sulfated polymer, polymerization and composition thereof.
  32. 32. the application of claim 31 wherein gives skin lasting antiviral efficacy.
  33. 33. the combinations thing is used for deactivation and/or kills virus and the application of the antimicrobial compositions of bacterium in preparation, comprises that above-mentioned composition comprises to the needs step of the mammal skin local application said composition of processing like this:
    (a) alcohol of the sterilization of 25%-75% by weight, the alcohol of said sterilization comprises one or more C 1-6Alcohol;
    (b) organic acid of 0.05%-6% by weight, it comprises (i) more than a kind of polybasic carboxylic acid with (ii) have the acid of the polymerization of a plurality of carboxyls, and
    (c) water,
    Wherein said composition has 5 or lower pH in the time of 25 ℃, and said composition reduces skin pH extremely less than 4 after dry on skin,
    Wherein organic acid comprises the polybasic carboxylic acid that contains 2-4 hydroxy-acid group; And randomly contain one or more hydroxyls, amino or both; The acid of polymerization is selected from phosphoric acid of the carboxylic acid of polymerization, the sulfonic acid of polymerization, Sulfated polymer, polymerization and composition thereof; Wherein said virus is nonenveloped virus, and said nonenveloped virus is deactivation.
  34. 34. the combinations thing is used for deactivation and/or kills virus and the application of the antimicrobial compositions of bacterium in preparation, comprises that above-mentioned composition comprises to the needs step of the mammal skin local application said composition of processing like this:
    (a) alcohol of the sterilization of 25%-75% by weight, the alcohol of said sterilization comprises one or more C 1-6Alcohol;
    (b) organic acid of 0.05%-6% by weight, it comprises (i) more than a kind of polybasic carboxylic acid with (ii) have the acid of the polymerization of a plurality of carboxyls, and
    (c) water,
    Wherein said composition has 5 or lower pH in the time of 25 ℃, and said composition reduces skin pH extremely less than 4 after dry on skin,
    Wherein organic acid comprises the polybasic carboxylic acid that contains 2-4 hydroxy-acid group; And randomly contain one or more hydroxyls, amino or both; The acid of polymerization is selected from phosphoric acid of the carboxylic acid of polymerization, the sulfonic acid of polymerization, Sulfated polymer, polymerization and composition thereof; Wherein said virus is rhinovirus, pico+ribonucleic acid+virus, adenovirus, rotavirus, herpes virus, Respiratory Syncytial Virus(RSV), coronavirus and enterovirus, and said rhinovirus, pico+ribonucleic acid+virus, adenovirus, rotavirus, herpes virus, Respiratory Syncytial Virus(RSV), coronavirus and enterovirus are deactivations.
  35. 35. the combinations thing is used for deactivation and/or kills virus and the application of the antimicrobial compositions of bacterium in preparation, comprises that above-mentioned composition comprises to the needs step of the mammal skin local application said composition of processing like this:
    (a) alcohol of the sterilization of 25%-75% by weight, the alcohol of said sterilization comprises one or more C 1-6Alcohol;
    (b) organic acid of 0.05%-6% by weight, it comprises (i) more than a kind of polybasic carboxylic acid with (ii) have the acid of the polymerization of a plurality of carboxyls, and
    (c) water,
    Wherein said composition has 5 or lower pH in the time of 25 ℃, and said composition at the thousands of skin pH that reduce after dry of skin to less than 4,
    Wherein organic acid comprises the polybasic carboxylic acid that contains 2-4 hydroxy-acid group; And randomly contain one or more hydroxyls, amino or both; The acid of polymerization is selected from phosphoric acid of the carboxylic acid of polymerization, the sulfonic acid of polymerization, Sulfated polymer, polymerization and composition thereof; Wherein said virus is the virus of acid labile, and the virus of said acid labile is deactivation.
  36. 36. the application of claim 34, wherein pico+ribonucleic acid+virus is deactivation.
  37. 37. the application of claim 34, wherein rhinovirus is deactivation.
  38. 38. the application of claim 34, wherein rotavirus is deactivation.
  39. 39. the combinations thing is used for being exposed to virus and bacterium is improved the application of the antimicrobial compositions of mammiferous holistic health through minimizing in preparation, may further comprise the steps:
    (a) to have virus and/or germ contamination the tendency the surface local application of said compositions and
    (b) make dry tack free,
    Above-mentioned composition comprises:
    (i) alcohol of the sterilization of 25%-75% by weight, the alcohol of said sterilization comprises one or more C 1-6Alcohol;
    The (ii) organic acid of 0.05%-6% by weight, it comprises more than a kind of polybasic carboxylic acid and the acid with polymerization of a plurality of carboxyls, and
    (iii) water,
    Wherein said composition has 5 or lower pH in the time of 25 ℃, and said composition reduces skin pH extremely less than 4 after dry on skin,
    Wherein organic acid comprises the polybasic carboxylic acid that contains 2-4 hydroxy-acid group, and randomly contains one or more hydroxyls, amino or both, and the acid of polymerization is selected from phosphoric acid of the sulfonic acid of the carboxylic acid of polymerization, polymerization, Sulfated polymer, polymerization and composition thereof.
  40. 40. the combinations thing is used for making individuality to avoid the application of the antimicrobial compositions of rhinovirus and rotavirus infection in preparation, comprises step from the amount above-mentioned composition that is enough to eliminate rhinovirus and rotavirus to the hand of individuality that use, above-mentioned composition comprises:
    (a) alcohol of the sterilization of 25%-75% by weight, the alcohol of said sterilization comprises one or more C 1-6Alcohol;
    (b) organic acid of 0.05%-6% by weight, it comprises (i) more than a kind of polybasic carboxylic acid with (ii) have the acid of the polymerization of a plurality of carboxyls, and
    (c) water,
    Wherein said composition has 5 or lower pH in the time of 25 ℃, and said composition reduces skin pH extremely less than 4 after dry on skin,
    Wherein organic acid comprises the polybasic carboxylic acid that contains 2-4 hydroxy-acid group, and randomly contains one or more hydroxyls, amino or both, and the acid of polymerization is selected from phosphoric acid of the sulfonic acid of the carboxylic acid of polymerization, polymerization, Sulfated polymer, polymerization and composition thereof.
  41. 41. the application of claim 40, wherein composition is before individuality is exposed to rhinovirus or rotavirus, to use.
  42. 42. the application of claim 40, wherein composition is repeatedly used within during 24 hours.
  43. 43. the application of claim 40, wherein composition is from flush away on hand.
  44. 44. the application of claim 40 wherein lets composition dries and staying on hand.
  45. 45. antimicrobial compositions comprises:
    (a) alcohol of the sterilization of 25%-75% by weight;
    (b) organic acid of 0.05%-6% by weight, it comprises that (i) is more than a kind of polybasic carboxylic acid with (ii) have the acid of the polymerization of a plurality of carboxyls; With
    (c) water,
    Wherein composition has 5 or lower pH in the time of 25 ℃,
    Wherein organic acid comprises the polybasic carboxylic acid that contains 2-4 hydroxy-acid group, and randomly contains one or more hydroxyls, amino or both, and the acid of polymerization is selected from phosphoric acid of the sulfonic acid of the carboxylic acid of polymerization, polymerization, Sulfated polymer, polymerization and composition thereof.
  46. 46. the composition of claim 45 further comprises the gelling agent of 0.01%-5% by weight.
  47. 47. the composition of claim 45, wherein organic acid is that amount with 0.5%-5% exists based on composition weight meter.
  48. 48. the composition of claim 45, wherein polybasic carboxylic acid comprises malic acid, citric acid, tartaric acid or its mixture, and the acid of polymerization comprises the homopolymers or the copolymer of acrylic or methacrylic acid.
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RU2366460C2 (en) 2009-09-10

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